Modulation of 8-Methoxypsoralen-Photoinduced Cutaneous Inflammatory Reactions by Various Chemotherapeutic Agents in vivo

Abstract— Exposure of albino rabbits to UVA-VIS (320-700 nm) radiation after the topical application of 8-methoxypsor-alen (8-MOP) cream is associated with acute cutaneous inflammatory reactions in situ. In the present studies the effects of various agents on 8-MOP plus light induced cutaneous inflammatory response viz. increase in vascular permeability (iVP), accumulation of polymorphonuclear leukocytes (aPMN) and erythema formation were investigated. The inflammatory reactions were induced by a single exposure of 8-MOP-sensitized sites to UVA-VIS (9.4J/cm²) light. Indomethacin, p-bromophenacyl bromide (BPAB), MK886 (trade name of Merck Sharpe & Dome), ibuprofen (IB), nordihydroguaiaretic acid (NDGA) or quinacrine were applied topically in cream base at various times prior to 8-MOP application. The iVP and aPMN were quantitated 24 h postirradiation using ^12SI-HSA and ⁵¹Cr-labeled PMN respectively, while erythema was graded visually. The rate of iVP, aPMN and erythema was inhibited almost completely by indomethacin (7.5-10%) when applied twice, 18 h and 3 h prior to 8-MOP. At lower concentrations of indomethacin (5%) iVP was inhibited whereas aPMN was augmented. The BPAB (0.25%) inhibited more than 90% of 8-MOP-photoinduced iVP and aPMN while there was partial reduction in erythema. The MK886 (0.1%) cream inhibited about 50% of iVP and aPMN but erythema persisted. The agents that are somewhat nonspecific such as IB, quinacrine and NDGA inhibited 8-MOP-photoinduced inflammation only marginally at the concentrations tested. The fact that iVP, aPMN and erythema can be dissociated suggests that there are independent variables in 8-MOP-photoinduced reactions, which involve multifactorial mechanisms probably controlled by different cell-signalling pathways and mediators.     

Exponential smoothing methods in pension funding

‘Smoothed-market’ methods are used by actuaries,when they value pension plan assets, in order to dampen thevolatility in contribution rates recommended to plan sponsors.A method involving exponential smoothing is considered. Thedynamics of the pension funding process is investigated in thecontext of a simple model where asset gains and losses emergeas a result of random rates of investment return and where thegains and losses are spread. It is shown that smoothing marketvalues up to a point does improve the stability of contributionsbut excessive smoothing is inefficient. It is also shown thatconsideration should be given to the combined effect of theasset valuation and gain and loss adjustment methods. Practicaland efficient combinations of gain/loss spreading periods andasset value smoothing parameters are suggested.     

Use of parabolic reflector to amplify in-air signals generated during impact-echo testing

The impact-echo method is a commonly used nondestructive testing technique for elastic plates in civil engineering. The impact-echo mode corresponds to the frequency at zero group velocity of S(1) Lamb mode. Recent development of the air-coupled impact-echo (ACIE) method introduces the possibility for rapid scanning of large structures and increases the practicality of in situ measurements. However, sensors used in ACIE are susceptible to ambient noise, which complicates in situ ACIE measurements. This letter presents the results of ACIE measurements taken using a parabolic reflector together with standard measurement microphones to increase the signal to noise ratio for ACIE measurements. The signal gain and effects of sensor location with respect to impact location are discussed.     

On age-period-cohort parametric mortality rate projections

An enhanced version of the Lee–Carter modelling approach to mortality forecasting, which has been extended to include an age modulated cohort index in addition to the standard age modulated period index, is described and tested for prediction robustness. Life expectancy and annuity value predictions, at pensioner ages and for various periods are compared, both with and without the age modulated cohort index, for the England & Wales male mortality experience. The simulation of prediction intervals for these indices of interest is discussed in detail.     

Nucleation of lead chromate from homogeneous solution

On the basis of the Christiansen-Nielsen model for nucleation, the nucleus of lead chromate precipitated from homogeneous solution has been found to consist of about five ions. The critical supersaturation values of solutions of lead chromate are dependent upon the method of filtration; however, a change in supersaturation of about 25 % is without effect on the size of the critical nucleus.     

A new approach to variable selection in least squares problems

The title Lasso has been suggested by Tibshirani (1996) as acolourful name for a technique of variable selection which requiresthe minimization of a sum of squares subject to an l₁ bound on the solution. This forces zero components in the minimizingsolution for small values of . Thus this bound can functionas a selection parameter. This paper makes two contributionsto computational problems associated with implementing the Lasso:(1) a compact descent method for solving the constrained problemfor a particular value of is formulated, and (2) a homotopymethod, in which the constraint bound becomes the homotopyparameter, is developed to completely describe the possibleselection regimes. Both algorithms have a finite terminationproperty. It is suggested that modified Gram-Schmidt orthogonalizationapplied to an augmented design matrix provides an effectivebasis for implementing the algorithms.     

Siderophore-Mediated Iron Uptake Promotes Yeast–Bacterial Symbiosis

In the present study, siderophore produced by the marine yeast Aureobasidium pullulans was characterized as hydroxamate by chemical and bioassays. The hydroxamate assignment was supported by the appearance of peaks at 1,647.21?C1,625.99?cm^?1 and at 1,435.04?cm^?1 in the infrared spectrum. The purified siderophore exhibited specific growth-promoting activity under iron-limited conditions for siderophore auxotrophic probiotic bacteria. Cross-utilization of siderophore indicates a symbiotic relationship between the yeast A. pullulans and the selected probiotic bacterial strains. Statistical optimization of medium components for improved siderophore production in A. pullulans was depicted by response surface methodology. The shift in UV?CVis spectroscopy indicates the photoreactive property and subsequent oxidative cleavage of purified siderophore on exposure to sunlight.     

Slow Passage Through the Nonhyperbolic Homoclinic Orbit of the Saddle-Center Hamiltonian Bifurcation

Slowly varying Hamiltonian systems, for which action is a well-known adiabatic invariant, are considered in the case where the system undergoes a saddle center bifurcation. We analyze the situation in which the solution slowly passes through the nonhyperbolic homoclinic orbit created at the saddle-center bifurcation. The solution near this homoclinic orbit consists of a large sequence of homoclinic orbits surrounded by near approaches to the autonomous nonlinear nonhyperbolic saddle point. By matching this solution to the strongly nonlinear oscillations obtained by averaging before and after crossing the homoclinic orbit, we determine the change in the action. If one orbit comes sufficiently close to the nonlinear saddle point, then that one saddle approach instead satisfies the nonautonomous first Painlevé equation, whose stable manifold of the unstable saddle (created in the saddle-center bifurcation) separates solutions approaching the stable center from those involving sequences of nearly homoclinic orbits.     

Modelling the joint distribution of competing risks survival times using copula functions

The problem of modelling the joint distribution of survival times in a competing risks model, using copula functions, is considered. In order to evaluate this joint distribution and the related overall survival function, a system of non-linear differential equations is solved, which relates the crude and net survival functions of the modelled competing risks, through the copula. A similar approach to modelling dependent multiple decrements was applied by Carriere [Carriere, J., 1994. Dependent decrement theory. Transactions, Society of Actuaries XLVI, 45-65] who used a Gaussian copula applied to an incomplete double-decrement model which makes it difficult to calculate any actuarial functions and draw relevant conclusions. Here, we extend this methodology by studying the effect of complete and partial elimination of up to four competing risks on the overall survival function, the life expectancy and life annuity values. We further investigate how different choices of the copula function affect the resulting joint distribution of survival times and in particular the actuarial functions which are of importance in pricing life insurance and annuity products. For illustrative purposes, we have used a real data set and used extrapolation to prepare a complete multiple-decrement model up to age 120. Extensive numerical results illustrate the sensitivity of the model with respect to the choice of copula and its parameter(s).